Is there a role fort drug treatments (chemotherapy or new molecular targeted drugs for squamous or basal cell carcinoma of the skin?

The vast majority of patients can be successfully managed with a variety of simple procedures, such as cryotherapy, curettage and electrodesiccation, topical treatments (5-fluorouracil, like Efudex or  imiquimod or Aldara, or simple surgical excision.

 Because of the rarity of metastatic basal cell and squamous cell cancers of the skin, the approach to systemic treatment is based primarily upon isolated case reports, with only a few small case series. In the published experience, cisplatin-based combinations appear to be the most active regimens. These regimens were in general adapted from those used for squamous cell cancers arising in other sites.

TARGETED THERAPIES  Targeted therapies are being developed for a range of malignancies, based upon an understanding of the underlying molecular pathogenesis. This approach has led to the development of vismodegib (Erivedge) , an inhibitor of the hedgehog signaling pathway, for basal cell carcinomas and these may eventually lead to the development of other agents for patients with advanced or metastatic skin cancers. The hedgehog signaling pathway can cause basal cell proliferation and tumor growth.

Vismodegib is an oral small molecule inhibitor of SMO, which thus blocks activation of the hedgehog pathway. Vismodegib was approved by the United States Food and Drug Administration for the treatment of advanced basal cell carcinoma, at a dose of 150 mg as a single oral daily dose.

The approval was based upon results of a non-randomized, single arm trial that included 104 patients with basal cell carcinoma with either metastatic (33 cases) or locally advanced disease (71 cases) that was not amenable to surgery or radiation therapy. The overall objective response rate in the 96 evaluable cases was 39 percent, with a median duration of response of 7.6 months in responding patients. The median time on treatment for all patients was more than 10 months.

Overall, the most frequent side effects were muscle spasms, taste abnormalities (dysgeusia and ageusia), and alopecia in 72, 66, and 64 percent of cases, respectively The most frequent grade 3 or 4 side effects were weight loss and fatigue, in 7 and 6 percent of cases, respectively.

EGFR pathway  Cetuximab (Erbitux) , a monoclonal antibody that targets the epidermal growth factor receptor (EGFR), has antitumor activity in patients with advanced squamous cell carcinoma of the skin, as initially suggested by case reports.

The potential role of cetuximab in treating advanced squamous cell carcinoma of the skin was studied prospectively in a phase II study that included 36 patients. The majority of patients had local-regional disease and only 8 percent had systemic metastases. Cetuximab was administered on its conventional weekly schedule (400 mg/m2 on week 1 and then 250 mg/m2 weekly). Eight partial and two complete responses were observed (objective response rate 28 percent in the intention to treat population), and 15 had stable disease for an overall disease control rate of 69 percent. Three patients were able to undergo complete resection of their tumor following treatment with cetuximab. The most common grade 3 and 4 toxicities included infection and tumor bleeding (eight and four cases, respectively). In line with what is observed in other malignancies, patients developing acneiform rash had a longer progression-free survival and a tendency for a longer survival (8.9 versus 4 months; p=.054).